Clinical pharmacology SYNOPSIS Clinical pharmacology comprises all aspects of the scientific study of drugs in man.. The drug and information 'explosion' of the past six decades combined
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SYNOPSIS
Clinical pharmacology comprises all aspects of
the scientific study of drugs in man Its
objective is to optimise drug therapy and it is
justified in so far as it is of practical use
Over recent years pharmacology has undergone great
expansion resulting from technology that allows the
understanding of molecular action and the capacity
to exploit this The potential consequences for
thera-peutics are enormous All cellular mechanisms
(normal and pathological), in their immense
com-plexity are, in principle, identifiable What seems
almost an infinity of substances, transmitters, local
hormones, cell growth factors, can be made, modified
and tested to provide agonists, partial agonists,
inverse agonists and antagonists And interference
with genetic disease processes is now possible
Increasingly large numbers of substances will deserve
to be investigated in therapeutics and used for
altering physiology to the perceived advantage (real
or imagined) of humans
But, with all these developments and their
poten-tial for good, comes capacity for harm, whether
inherent in the substances or as a result of human
misapplication
Successful use of the power conferred (by
bio-technology in particular) requires understanding of
the enormous complexity of the consequences of
interference Willingness to learn the principles of
pharmacology and how to apply them in individual
circumstances of infinite variety is vital to success without harm: to maximise benefit and minimise risk All these issues are the concern of clinical pharmacologists and are the subject of this book The drug and information 'explosion' of the past six decades combined with medical need has called into being the discipline, clinical pharmacology The discipline is now recognised as both a health care and an academic specialty; indeed, no med-ical school can now be considered complete with-out a department or subdepartment of Clinical Pharmacology
The clinical pharmacologist's role is to provide
facts and opinions that are useful for optimising the
treatment of patients Therapeutic success with drugs
is becoming more and more dependent on the user having at least an outline understanding of both pharmacodynamics and pharmacokinetics And this outline is quite simple and easy to acquire However humane and caring doctors may be, they cannot dispense with scientific skill
• the general aspects of rational, safe and effective drug therapy
• drug therapy of individual diseases
• introduction of new medicines.
Pharmacology is commonly practised in concert with other clinical specialties More detailed aspects comprise:
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1 Pharmacology
• Pharmacodynamics: how drugs, alone and in
combination, affect the body (young, old,
well, sick)
• Pharmacokinetics: absorption, distribution,
metabolism, excretion or, how the body, well
or sick, affects drugs
2 Therapeutic evaluation
• Whether a drug is of value
• How it may best be used
• Formal therapeutic trials
• Surveillance studies for both efficacy and
safety (adverse effects):
pharmacoepidemiology and
pharmacovigilance
3 Control
• Rational prescribing and formularies
• Official regulation of medicines
• Social aspects of the use and misuse of
medicines
• Pharmacoeconomics
If it is desired to single out a pioneer clinical
(1899-1972) of Cornell University, USA, whose
in-fluential studies in the 1930s showed us how to be
clinical pharmacologists In 1952 he wrote in a
seminal article:
1 Gold H 1952 'The proper study of mankind is man',
American Journal of Medicine 12: 619 The title is taken from
An Essay on Man by Alexander Pope (English poet,
1688-1744); the whole passage is relevant to modern clinical
pharmacology and drug therapy; it is best read aloud
whether the reader be alone or in company
Know then thyself, presume no God to scan,
The proper study of mankind is man,
Placed on this isthmus of a middle state,
A being darkly wise, and rudely great:
With too much knowledge for the sceptic side,
With too much weakness for the stoic's pride,
He hangs between; in doubt to act or rest;
In doubt to deem himself a god or beast;
In doubt his mind or body to prefer;
Born but to die, and reas'ning but to err;
Alike in ignorance, his reason such,,
Whether he thinks too little or too much;
Chaos of thought and passion, all confused;
Still by himself abused, or disabused;
Created half to rise, and half to fall;
Great lord of all things, yet a prey to all;
Sole judge of truth, in endless error hurled;
The Glory, jest and riddle of the world!
a special kind of investigator is required, one whose training has equipped him not only with the principles and technics of laboratory
pharmacology but also with knowledge of clinical medicine
Clinical scientists of all kinds do not differ fundamentally from other biologists; they are set apart only to the extent that there are special difficulties and limitations, ethical and practical, in seeking knowledge from man.2
Pharmacology is the same science whether animal
or man is investigated The need for it grows rapidly
as not only scientists, but now the whole community, can see its promise of release from distress and premature death over yet wider fields The con-comitant dangers of drugs (fetal deformities, adverse reactions, dependence) only add to the need for the systematic and ethical application of science to drug development, evaluation, and use, i.e clinical pharmacology
GUIDETO FURTHER READING
Brater D C, Daly W J 2000 Clinical pharmacology in the middle ages: principles that presage the 21st century Clinical Pharmacology and Therapeutics 67: 447-450
Breckenridge A1995 Science, medicine and clinical pharmacology British Journal of Clinical Pharmacology 40:1-9
Breckenridge A1999 Clinical pharmacology and drug regulation British Journal of Clinical
Pharmacology 47: 11-12 Dollery C T 1996 Clinical pharmocology: future prospects for the discipline British Journal of Clinical Pharmacology 42:137-141
2 Self-experimentation has always been a feature of clinical pharmacology A survey of 250 members of the Dutch Society of Clinical Pharmacology evoked 102 responders of whom 55 had done experiments on themselves (largely for convenience) (van Everdingen et al 1990 Lancet 336:1448) A spectacular example occurred at the 1983 meeting of the American Urological Association at Las Vegas, during a lecture on pharmacologically-induced penile erection, when the lecturer stepped out from behind the lectern to
demonstrate personally the efficacy of the technique (Zorgmotti A W 1990 Lancet 336: 1200)
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Grahame-Smith D G 1991 Clinical Pharmacology
Roles and responsibilities in academic research
British Journal of Clinical Pharmacology 32:151
Laurence D R 1989 Ethics and law in clinical
pharmacology British Journal of Clinical
Pharmacology 27: 715-722
Reidenberg M M 1999 Clinical pharmacology: the scientific basis of therapeutics Clinical Pharmacology and Therapeutics 66: 2-8 Walley T 1995 Drugs, money and society British Journal of Clinical Pharmacology 39: 343-345
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